Size changes of alveoli and small airways are critically involved in the development of chronic lung disease; yet there is no in vivo method of determining and differentiating these dimensions. Calculations presented here show that alveolar and small airway size have different effects on the pattern of aerosol deposition as a function of depth of inspiration. We thus hypothesize it is possible to estimate and distinguish these lung dimensions on the basis of deposition experiments. The proposed method consists of inspiration of a small bolus of monodisperse aerosol, followed by a period of breathholding, followed by exhalation. The recovery, defined as the ratio of the number of particles inspired to those expired, is measured for a series of inspiration depths. Alveolar and small airway dimensions are determined by fitting the results to a multicompartment model of aerosol recovery. Model assumptions on aerosol penetration will be checked against a penetration index, measured in isolated lungs using a radiolabelled aerosol. The hypothesis will be tested in two ways: First, aerosol estimates of alveolar and small airway dimensions in isolated lungs will be compared to: 1) direct visualization of subpleural alveoli using photomicroscopy, 2) functional tests (static pressure-volume curve and anatomical dead space) which are indirectly related to alveolar and airway dimensions, 3) morphometric measurements on the fixed, sectioned specimen. Second, aerosol estimates of lung dimensions will be made in vivo before and after administering pharmacologic agents to effect size changes in lung structures. Aerosol measurement of lung structure dimensions is a non-invasive technique, applicable in humans. Its validation will facilitate the study of chronic lung disease both clinically and in experimental animals.